Core A: Cell Model and Evaluation Core

项目总结/摘要：P30核心A 分化良好的原代人气道上皮细胞和可以与它们一起使用的测定法是一种新的方法。 用于理解上皮生物学的工具模型，并高度预测临床中的体内结果 审判原代细胞可以与容易转化为体内气道功能测定的方法一起使用， 包括测量CFTR活性或其他离子转运蛋白、气道表面液体深度和粘液 水化和粘液粘度和运输。初级气道细胞进一步提供了一个极好的模型， 检查气道上皮炎症的生物学，这是囊性纤维化（CF）发病机制的关键 肺病。核心A的目的是支持众多P30研究者的研究， 细胞培养系统，并协助建立和创新的分析，可用于表征细胞 应答 核心A执行具体目标中概述的三个主要功能。首先，核心A采购，增长， 分布来自CF和非CF供体的分化良好的原代人气道上皮细胞。这包括 来自肺移植、手术切除的鼻组织和在UAB获得的鼻刷的细胞样本 and from a large大array阵列of collaborating合作centers中心.新的扩展和分化技术的检查 也是核心的关键功能。第二，核心A进行功能解剖成像， 1微米分辨率光学相干断层扫描（μ OCT）的体外气道上皮细胞（人的原代细胞 或非人来源）和离体（人来源的完整全层气管或主干支气管，或 来自CF动物模型的可比较组织，因此与核心B接合）。μ OCT允许研究者 探索粘液流动和粘液纤毛的相互作用，并被指定为国家核心，由于其独特的， 重要的能力。第三，核心A执行并协助CFTR活动和表达的测量。在 除了传统的CFTR功能测定（例如，Ussing室）外，Core还支持创新的 电导测定和先进的PCR技术用于研究CFTR和其他蛋白质表达。 核心A促进跨学科的合作研究，提供超出专业知识的资源， 个人研究实验室，促进思想和实验策略的共享，协助技术 排除故障，维护P30人员大量使用的必要设备， 超越。通过最大限度地减少个别CF调查员的重复工作， 集中采购和使用设备、试剂和供应品，以及维持一个 人类上皮组织的储存库。总体而言，核心A提供了重要的专业知识和资源， 帮助P30研究人员，促进上皮细胞培养和创新检测的进步，以了解 CFTR发病机制和支持合理的药物发现。

PROJECT SUMMARY / ABSTRACT: P30 CORE A Well-differentiated primary human airway epithelial cells and the assays that can be used with them are an instrumental model for understanding epithelial biology and are highly predictive of in vivo results in clinical trials. Primary cells can be used with methodologies that translate readily to assays of airway function in vivo, including measures of CFTR activity or other ion transporters, airway surface liquid depth and mucus hydration, and mucus viscosity and transport. Primary airway cells further provide an excellent model for examining the biology of airway epithelial inflammation, which is key to the pathogenesis of cystic fibrosis (CF) lung disease. The purpose of Core A is to support the research of numerous P30 investigators that involves cell culture systems and to assist with established and innovative assays available to characterize cellular responses. Core A carries out three main functions as outlined in the Specific Aims. First, Core A procures, grows, and distributes well-differentiated primary human airway epithelial cells from CF and non-CF donors. This includes samples of cells from lung transplants, surgically excised nasal tissue, and nasal brushings obtained at UAB and from a large array of collaborating centers. Examination of novel expansion and differentiation techniques for primary cells is also a key function of the Core. Second, Core A conducts functional anatomic imaging of airway epithelia by 1-micron resolution Optical Coherence Tomography (μOCT) in vitro (primary cells of human or non-human origin) and ex vivo (intact full-thickness trachea or mainstem bronchi of human origin or comparable tissues from CF animal models, thus interfacing with Core B). μOCT allows for investigators to explore mucus flow and mucociliary interactions and is designated as a National Core due to its unique and important capabilities. Third, Core A performs and assists with measures of CFTR activity and expression. In addition to traditional assays of CFTR function (e.g, Ussing chambers), the Core supports innovative conductance assays and advanced PCR technology for investigating CFTR and other protein expression. Core A facilitates interdisciplinary collaborative research, provides resources that are beyond the expertise of individual research laboratories, fosters the sharing of ideas and experimental strategies, assists with technical troubleshooting, and maintains essential equipment that is and will be heavily utilized by P30 personnel and beyond. Cost savings are achieved by minimizing duplicate efforts of individual CF investigators, by the centralized purchase and usage of equipment, reagents, and supplies, as well as by maintaining a central repository for human epithelial tissue. On the whole, Core A provides significant expertise and resources to aid P30 investigators, fostering advancement of epithelial cell culture and innovative assays to understand CFTR pathogenesis and support rational drug discovery.